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G. Oderda [1] A. Rapa [2] R. Boldorini [3] C. Bozzola [2] A. Zavallone [2] L. Strigini [2] M.Y. Shcherbakova [4] P. Shcherbakov [4] [14/01] [*] Non-invasive Tests to diagnose [...]

Ciprofloxacin is a widely used fluoroquinolone for the treatment of patients with complicated and uncomplicated infections. With rare exceptions, only immune-mediated interstitial nephritis was described, with direct renal damage reported only in case of overdose. Experimental studies indicated that crystalluria may be associated with the administration of this drug, but the likelihood that ciprofloxacin crystal nephropathy would occur in humans was believed to be very low on the basis of previous data showing that ciprofloxacin crystalluria depended on a urine pH greater than 6.8. However, we report 2 cases of ciprofloxacin crystal-induced nephropathy with a clinical pattern of acute reversible tubular damage and intratubular crystals identical to that previously described in elderly patients treated with ciprofloxacin dosages within therapeutic schedules. Crystals in the tubules were negative for both the von Kossa stain for phosphates and alizarin red stain for calcium.Copyright © 2007 by National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Few data are available on childhood Helicobacter pylori gastritis and its relation to age. We investigated pathologic changes in gastric mucosa of children and adults of different age. Materials and Methods: Gastric mucosa specimens of 74 children (age range 1-18 years) were compared with those of 51 adults (age range, 2970). All had H. pylori gastritis without peptic ulcer. Morphologic analysis according to the Updated Sydney System and morphometric analysis to determine inflammatory cell the density (cell/mm2) were performed. Results: Pangastritis was less frequent in children (92% vs. 100% in adults, p = 0.03) and morphologic scores were significantly lower in children than in adults (4 vs. 6, p = 0.0002 in the antrum; 4 vs. 7, p = 0.000 in the corpus). Children had lower density of all cell types, and lower frequency of neutrophils' infiltration than adults in the corpus (54% vs. 78%, p < 0.009). In both groups a significant correlation was found between morphologic scores and neutrophils' density in the antrum (r = 0.608, p < 0.0001 in children; r = 0.881, p < 0.0001 in adults) and in the corpus (r = 0.780, p < 0.0001 in children; r = 0.908, p < 0.0001 in adults). Atrophic gastritis (4%) and intestinal metaplasia (1%) were exceptional in children and significantly more frequent in adults. Conclusions: Inflammation in childhood H. pylori gastritis is milder than in adults because of lower neutrophil prevalence and density in gastric mucosa. Pangastritis is less frequent in children but a constant finding in adults. Atrophy and intestinal metaplasia are rare in childhood gastritis. There is a good correlation between morphologic scores and morphometric evaluation of H. pylori gastritis both in children and adults. The Updated Sydney System seems suitable for evaluation of gastritis also in children. [ABSTRACT FROM AUTHOR]

Smartphone-based technology is increasingly used in veterinary medicine as a complementary tool for cardiac auscultation and ECG recording. This prospective observational study evaluates a digital stethoscope (DS) that consists of simultaneous phonocardiographic and one-lead ECG recording (dECG) in adult horses, comparing it with auscultation using a conventional stethoscope (CS) and reference base-apex ECG (rECG). A total of 104 horses underwent cardiac auscultation using CSs and DSs to detect arrhythmias and murmurs. Audio and dECG were acquired using the DS. The rECG tracings were also recorded. All ECG tracings were blindly evaluated for interpretability, measurements, and diagnosis. The Shapiro-Wilk test was used to assess the data distribution. Weighted Cohen's κ and Bland Altman plot analysis were applied to verify the agreement between reference vs. smartphone-based methods. Almost perfect agreement was found in detecting murmurs and/or arrhythmias between auscultation with the CS and DS, and between CS auscultation and re-listening to DS audio. Perfect agreement was observed between re-listening to DS audio and DS auscultation and in detecting murmur timing between CS and DS auscultation. Almost perfect agreement was found between rECG and dECG in detecting bradycardia, tachycardia, or normal heart rate (HR) and for P-wave polarity. The lack of variability with both methods for QRS polarity prevented statistical analyses from being performed. Fair agreement was found in the assessment of the presence of artifact. In conclusion, the DS reliably detected heart murmurs and arrhythmias through direct auscultation and re-listening to recordings, and accurately evaluated HR, wave and interval measurements, P-wave and QRS-complex polarities in adult horses., Competing Interests: Declarations. Ethics approval: The experiments were conducted following the Guide for the Care and Use of Animals in Research and Teaching, after the approval of the Ethic Committee of the University of Pisa (OPBA n. 53/2020). Consent to participate: All authors consent to participation in this publication. Consent to publish: All authors consent to publication of the manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Exercise-Induced Pulmonary Hemorrhage (EIPH) is a common pulmonary disease among racehorses, diagnosed by the detection of blood in the trachea after strenuous exercise or the presence of hemosiderophages in the bronchoalveolar lavage fluid (BALF). Although the latter is considered the most sensitive method to diagnose EIPH, it is perceived as a less practical and more invasive procedure compared to tracheal wash (TW) collection among racehorse trainers. The present retrospective study aimed to verify the agreement between Tracheal wash and BALF cytology in assessing EIPH in racehorses. For this purpose, cytological data from 172 patients regarding hemosiderophage percentage, hemosiderin score, and percentage of recent, intermediate, and old EIPH were reviewed, and the simplified Total Hemosiderin Score (sTHS) was calculated. Non-parametric statistical tests were used to assess the difference and the correlation between TW and BALF. The two cytological methods strongly agreed in evaluating EIPH in racehorses for hemosiderophage percentage (ρ = 0.89, p < 0.001), hemosiderin score (k = 0.63, p < 0.001), sTHS (ρ = 0.87, p < 0.001), percentage of recent EIPH (ρ = 0.95, p < 0.001), intermediate EIPH (ρ = 0.92, p < 0.001), and old EIPH (ρ = 0.85, p < 0.001). In conclusion, TW showed to be a reliable method, which might substitute BALF in assessing EIPH in racehorses.

Objective: The research aimed to determine whether and which radiomic features from breast dynamic contrast enhanced (DCE) MRI could predict the presence of BRCA1 mutation in patients with triple-negative breast cancer (TNBC)., Material and Methods: This retrospective study included consecutive patients histologically diagnosed with TNBC who underwent breast DCE-MRI in 2010-2021. Baseline DCE-MRIs were retrospectively reviewed; percentage maps of wash-in and wash-out were computed and breast lesions were manually segmented, drawing a 5 mm-Region of Interest (ROI) inside the tumor and another 5 mm-ROI inside the contralateral healthy gland. Features for each map and each ROI were extracted with Pyradiomics-3D Slicer and considered first separately (tumor and contralateral gland) and then together. In each analysis the more important features for BRCA1 status classification were selected with Maximum Relevance Minimum Redundancy algorithm and used to fit four classifiers., Results: The population included 67 patients and 86 lesions (21 in BRCA1-mutated, 65 in non BRCA-carriers). The best classifiers for BRCA mutation were Support Vector Classifier and Logistic Regression in models fitted with both gland and tumor features, reaching an Area Under ROC Curve (AUC) of 0.80 (SD 0.21) and of 0.79 (SD 0.20), respectively. Three features were higher in BRCA1-mutated compared to non BRCA-mutated: Total Energy and Correlation from gray level cooccurrence matrix, both measured in contralateral gland in wash-out maps, and Root Mean Squared, selected from the wash-out map of the tumor., Conclusions: This study showed the feasibility of a radiomic study with breast DCE-MRI and the potential of radiomics in predicting BRCA1 mutational status., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The donkey has always been a notable working animal and its importance as a companion animal has been growing over the last few years. However, there are only a few studies about cardiology in this species. Therefore, this study aimed to evaluate the influence of age, sex, training, and bodyweight on cardiac dimension in mixed-breed donkeys. Forty-five clinically and para-clinically healthy mixed-breed donkeys were included, and B-mode and M-mode echocardiographic measurements were recorded. Multivariate linear regression analysis was performed to identify the effect of age, sex, bodyweight, and training on cardiac measurements. Most of the echocardiographic measurements showed a strong statistically significant correlation with bodyweight. Linear regression analysis between echocardiographic measurements and bodyweight was performed to obtain the values of the intercept and slope of the linear equation to calculate the echocardiographic measurements as a function of bodyweight. This is the first study reporting a strong linear correlation between echocardiographic measurements and bodyweight and reporting a correlation between training and echocardiographic parameters in donkeys, suggesting that this variable should be considered when assessing cardiac dimensions in these animals., (© 2024. The Author(s).)

The digital stethoscope (DS) is a cost-effective single-lead digital stethoscope that allows simultaneous electrocardiographic (ECG) and phonocardiographic recordings on a smartphone. Despite its application in small animals and horses, there are currently no studies on its use in donkeys. The aim of this study was to evaluate the use of a new smartphone-based DS device in recording ECG tracings in donkeys. Standard base-apex lead ECG (sECG) and single-lead DS ECG (dECG) were simultaneously recorded for at least 30 s. Both sECG and dECG tracings were analysed by the same operator, recording heart rate, ECG waves and intervals, and the presence and duration of artefacts. Thirty-seven donkeys were included. The dECG tracings were interpretable in all the animals (100 %). The results showed perfect agreement between the sECG and dECG data for the classification of heart rhythm and P-wave polarity. Strong agreement was found in the evaluation of heart rate calculated manually and automatically by the smartphone app, QRS complex polarity, T wave polarity, and duration of the PR interval. However, no agreement was found in the evaluation of P wave duration, QRS complex duration and amplitude, and T wave duration and amplitude. In conclusion, although this is only a preliminary study, the DS was a valid, practical, and easy to use electrocardiographic tool for recording good-quality ECG tracings to assess the ECGs of donkeys in the field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In racehorses, the associations between physiological parameters obtained by exercise testing and racing results have been questioned. We hypothesized that fitness variables measured during a treadmill incremental test may be related with racing outcomes and lifetime career. Our study aimed to investigate the role of fitness parameters obtained during a treadmill test in performance evaluation and career prediction in poorly performing Standardbreds, through a retrospective review of the clinical records of 245 trotters that underwent an incremental treadmill test. Several fitness parameters were assessed, and their correlations with racing data (number of starts, wins and placings) in the 3 months before and 6 months after examination were evaluated; moreover their associations and predictive power for lifetime racing results and earnings were considered. The associations between fitness parameters and measures of racing performance as well as the associations between racing results over time were evaluated by Spearman's correlation in the whole population and in different age groups. Multivariate regression models predicting the total number of starts, wins and earnings based on fitness parameters were constructed, controlling for age, weight, and sex. Maximum speed and the speed at the aerobic threshold were the parameters correlated with the most racing results, in the three evaluation periods (3 months before, 6 months after, lifetime). Other parameters predictive of career outcomes were maximum blood lactate concentration and maximum hematocrit. Interestingly, in 2-year-old Standardbreds, the only parameters correlated with racing results were maximum hematocrit and minimum pH, suggesting they may reflect individual potential. Both the racing results obtained before and after examination were predictive of lifetime career, with those following hospitalization being more strongly correlated. In conclusion, parameters obtained during treadmill tests both reflect the racing outcomes and the career potential., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lo Feudo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Poor performance in racehorses is commonly associated with subclinical diseases. This study aims to evaluate the associations between medical disorders and racing results in Standardbred trotters. The clinical records of 248 poorly performing Standardbreds were retrospectively reviewed, and their racing results were extracted from an online database, concerning the periods 3 months before and 6 months after hospitalization and the entire lifetime. Generalized linear models were used to evaluate the effects of different disorders on racing outcomes. Airway neutrophilia was associated with limiting lifetime starts and wins pre- and post-hospitalization, while mastocytosis was associated with less wins in the post-hospitalization period. Therefore, lower airway inflammation showed both short- and long-term impacts on racing performance. Severe upper airway obstructions and gastric ulcers showed associations with less placings in the post-discharge period but no long-term influence on performance. The significance of exertional rhabdomyolysis was indeterminable, yet interference with the number of starts in the post-discharge period was reported and associated with lower total career earnings. Exercise-induced pulmonary hemorrhage and cardiac arrhythmias were not associated with worse racing outcomes: therefore, their role in poor performance remains unclear.

The liver capacity to recover from acute liver injury is a critical factor in the development of acute liver failure (ALF) caused by viral infections, ischemia/reperfusion or drug toxicity. Liver healing requires the switching of pro-inflammatory monocyte-derived macrophages(MoMFs) to a reparative phenotype. However, the mechanisms involved are still incompletely characterized. In this study we investigated the contribution of T-lymphocyte/macrophage interaction through the co-stimulatory molecule Inducible T-cell co-stimulator (ICOS; CD278) and its ligand (ICOSL; CD275) in modulating liver repair. The role of ICOS/ICOSL dyad was investigated during the recovery from acute liver damage induced by a single dose of carbon tetrachloride (CCl 4 ). Flow cytometry of non-parenchymal liver cells obtained from CCl 4 -treated wild-type mice revealed that the recovery from acute liver injury associated with a specific up-regulation of ICOS in CD8 + T-lymphocytes and with an increase in ICOSL expression involving CD11b high /F4-80 + hepatic MoMFs. Although ICOS deficiency did not influence the severity of liver damage and the evolution of inflammation, CCl 4 -treated ICOS knockout (ICOS -/- ) mice showed delayed clearance of liver necrosis and increased mortality. These animals were also characterized by a significant reduction of hepatic reparative MoMFs due to an increased rate of cell apoptosis. An impaired liver healing and loss of reparative MoMFs was similarly evident in ICOSL-deficient mice or following CD8 + T-cells ablation in wild-type mice. The loss of reparative MoMFs was prevented by supplementing CCl 4 -treated ICOS -/- mice with recombinant ICOS (ICOS-Fc) which also stimulated full recovery from liver injury. These data demonstrated that CD8 + T-lymphocytes play a key role in supporting the survival of reparative MoMFs during liver healing trough ICOS/ICOSL-mediated signaling. These observations open the possibility of targeting ICOS/ICOSL dyad as a novel tool for promoting efficient healing following acute liver injury., Competing Interests: UD, EB, and LCG are listed as inventors on the patent PCT/IB2019/050154 “Novel anti-tumor therapeutic agents”. EB, UD, and LCG are founders of an University Spin-off (NOVAICOS). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ramavath, Gadipudi, Provera, Gigliotti, Boggio, Bozzola, Albano, Dianzani and Sutti.)

Introduction: Acute kidney injury (AKI) has been described as a common complication of cardiac surgery in pediatric patients, whose impact on morbidity and mortality has been documented. Its incidence has been estimated to be approximately 40 % in this patient group. The objective of this study was to estimate the incidence of AKI in patients who underwent cardiovascular surgery and to define associated risk factors and the impact of AKI on the parameters of the postoperative course., Population and Methods: This was a retrospective, observational study of pediatric patients who underwent cardiovascular surgery between January 2015 and December 2017 at Hospital Británico de Buenos Aires. The incidence of AKI was defined as per the Kidney Disease: Improving Global Outcomes criteria, based on pre- and post-operative blood creatinine levels and urine output., Results: A total of 125 patients were included. Of them, 35 % developed AKI. The analysis of risk factors showed a statistically significant difference for the administration of vancomycin and thiazide diuretics, red blood cell transfusion requirement, extracorporeal circulation pump time, clamp time, maximal intraoperative lactate level, minimum temperature, and delayed chest closure. In relation to the parameters of the post-operative course, we observed a longer hospital stay, higher inotropic requirement, more days of mechanical ventilation, bleeding, and neurological complications., Conclusion: In this study, the incidence of AKI was 35 %. Modifiable and non-modifiable associated risk factors were defined and a greater rate of complications was observed in patients who developed AKI., Competing Interests: The authors report no conflicts of interest in this work., (Sociedad Argentina de Pediatría.)

Recent evidence implicates adaptive immunity as a key player in the mechanisms supporting hepatic inflammation during the progression of nonalcoholic fatty liver disease (NAFLD). In these settings, patients with NAFLD often show an increase in the circulating levels of antibodies against oxidative stress-derived epitopes (OSE). Nonetheless, the actual role of humoral immunity in NAFLD is still unclear. This study investigates the contribution of B-lymphocytes to NAFLD evolution. B-lymphocyte immunostaining of liver biopsies from NAFLD patients showed that B-cells were evident within cell aggregates rich in T-lymphocytes. In these subjects, B/T-lymphocyte infiltration positively correlated with both circulating IgG targeting oxidative stress-derived epitopes (OSE) and interferon-γ (IFN-γ) levels. Furthermore, high prevalence of lymphocyte aggregates identified patients with more severe lobular inflammation and fibrosis. In mouse models of NAFLD, the onset of steatohepatitis was characterized by hepatic B2-lymphocytes maturation to plasma cells and by an elevation in circulating anti-OSE IgG titers. B-cell responses preceded T-cell activation and were accompanied by the up-regulation in the hepatic expression of B-cell Activating Factor (BAFF). Selective B2-cell depletion in mice over-expressing a soluble form of the BAFF/APRIL receptor Transmembrane Activator and Cyclophilin Ligand Interactor (TACI-Ig) prevented plasma cell maturation and Th-1 activation of liver CD4 + T-lymphocytes. Furthermore, TACI-Ig mice showed milder steatohepatitis and a decreased progression to fibrosis. Similarly, mice treatment with the BAFF-neutralizing monoclonal antibody Sandy-2 prevented hepatic B2-cell responses and ameliorated steatohepatitis. From these data we conclude that B2-lymphocyte activation is an early event in NAFLD evolution and contributes to the disease progression through the interaction with T-cells. Furthermore, combined clinical and experimental data suggest that elevated circulating anti-OSE IgG can identify a subset of NAFLD patients in whom adaptive immunity has a relevant role in the disease evolution toward fibrosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Mechanisms underlying progression of nonalcoholic fatty liver disease (NAFLD) are still incompletely characterized. Hypoxia and hypoxia-inducible factors (HIFs) have been implicated in the pathogenesis of chronic liver diseases, but the actual role of HIF-2α in the evolution of NAFLD has never been investigated in detail. In this study, we show that HIF-2α is selectively overexpressed in the cytosol and the nuclei of hepatocytes in a very high percentage (>90%) of liver biopsies from a cohort of NAFLD patients at different stages of the disease evolution. Similar features were also observed in mice with steatohepatitis induced by feeding a methionine/choline-deficient diet. Experiments performed in mice carrying hepatocyte-specific deletion of HIF-2α and related control littermates fed either a choline-deficient L-amino acid-defined or a methionine/choline-deficient diet showed that HIF-2α deletion ameliorated the evolution of NAFLD by decreasing parenchymal injury, fatty liver, lobular inflammation, and the development of liver fibrosis. The improvement in NAFLD progression in HIF-2α-deficient mice was related to a selective down-regulation in the hepatocyte production of histidine-rich glycoprotein (HRGP), recently proposed to sustain macrophage M1 polarization. In vitro experiments confirmed that the up-regulation of hepatocyte HRGP expression was hypoxia-dependent and HIF-2α-dependent. Finally, analyses performed on specimens from NAFLD patients indicated that HRGP was overexpressed in all patients showing hepatocyte nuclear staining for HIF-2α and revealed a significant positive correlation between HIF-2α and HRGP liver transcript levels in these patients., Conclusions: These results indicate that hepatocyte HIF-2α activation is a key feature in both human and experimental NAFLD and significantly contributes to the disease progression through the up-regulation of HRGP production. (Hepatology 2018;67:2196-2214)., (© 2017 by the American Association for the Study of Liver Diseases.)

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the procedure of choice for the cytologic diagnosis of pancreatic masses. The specificity of EUS-FNA approaches 100%, but the sensitivity is still low, and the high rate of indeterminate (atypical and suspicious) and false-negative results needs improvement. KRAS gene is frequently mutated in pancreatic ductal adenocarcinoma (PDAC) (up to 90%), and mutation analysis of KRAS has been proposed as diagnostic biomarker of PDAC. In most laboratories, KRAS mutation testing is performed by Sanger sequencing or real time-quantitative polymerase chain reaction (RT-qPCR), but these methods may give false-negative results in routine samples, mainly due to low cellularity. In order to increase the sensitivity of EUS-FNA, we propose a sequential approach for detecting KRAS mutations using mutant enriched-PCR (ME-PCR, sensitivity up to 0.1%) in cytologically indeterminate and negative samples tested wild-type by RT-qPCR. EUS-FNA specimens from 107 patients with pancreatic masses (51 males, 56 females, mean age 67 years) were cytologically examined. According to the Papanicolaou Society of Cytopathology guidelines, 50 cases (47%) were classified malignant, 15 (14%) suspicious, 13 (12%) atypical and 10 (9%) negative for malignancy; 18 cases (17%) were non-diagnostic. The overall specificity and sensitivity of cytological examination were 100% and 61%, respectively, when only negative and positive cases were considered; when atypical and suspicious were added to positive cases, the sensitivity increased to 95.1% and the specificity decreased to 85.7%. In all the cases, DNA was extracted from the cell-block and KRAS mutations were investigated by RT-qPCR, followed by ME-PCR in non-amplifiable and negative cases. The overall sensitivity and specificity of KRAS mutation testing alone were 79.3% and 100%; when KRAS mutation testing was performed in indeterminate and negative cytology, the sensitivity increased to 90% with specificity to 100%. Our data indicate that conventional cytology from EUS-FNA samples is highly specific for the diagnosis of pancreatic cancer. Indeterminate and negative cases need to be screened for KRAS mutations; this two-step approach may greatly improve the diagnostic accuracy of this method., (Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Unlabelled: A standardized histologic definition and classification of the patterns of renal tumor pseudocapsular invasion (RTPI) in renal cell carcinoma (RCC) is not available. We classified RTPI into 2 main histologic patterns: expansive and infiltrative RTPI. Patients with organ-confined RCC and infiltrative RTPI had a greater risk of cancer-specific death and might require stricter postoperative surveillance strategies., Introduction: A standardized histologic definition and classification of patterns of renal tumor pseudocapsular invasion (RTPI) in renal cell carcinoma (RCC) is not available. The aim of the present study was to propose a classification of RTPI patterns and assess their correlation with other pathologic features and prognosis., Patients and Methods: The renal tumor pseudocapsule was assessed by 2 expert genitourinary pathologists on the histologic slides of 190 specimens from radical nephrectomy performed for organ-confined (pT1-pT2) RCC. The histologic patterns of RTPI were classified and described. The association between the RTPI patterns and other pathologic features was assessed. The Kaplan-Meier method was used to calculate the survival functions, and Cox regression models were used to assess the predictors of cancer-specific survival., Results: RTPI was classified into 2 main histologic patterns (expansive and infiltrative). Expansive and infiltrative RTPI was observed in 39.5% and 51.6% of cases, respectively. A significant association between the RTPI pattern and Fuhrman grade (P = .006) and RCC histologic subtype (P = .034) was detected. Patients with infiltrative pseudocapsular invasion had significantly poorer 5- and 10-year cancer-specific survival rates than patients with expansive invasion or no invasion (93.6% vs. 98.9% and 84.9% vs. 93%, respectively; P = .039). The presence of infiltrative pseudocapsular invasion was a significant predictor of cancer-specific survival (hazard ratio 4.38, 95% confidence interval 1.04-20.27)., Conclusion: An expansive and an infiltrative RTPI pattern can be described. In our study, patients with organ-confined RCC and an infiltrative RTPI pattern had a greater risk of cancer-specific death and might require stricter postoperative surveillance strategies., (Copyright © 2016 Elsevier Inc. All rights reserved.)